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Biomedical subjects

A Gairard

Publications and source records attributed to A Gairard.

At least 37 records · Page 2Linked to original sources
PubMed1993

[Genetic hypertension in the rat is partially dependent of parathyroid glands. Results of a crossed transplantation trial].

The parathyroid hypertensive factor (PHF) is present in the plasma of SHR rats. The authors of this study set out to determine whether this factor was also present in the Lyon (LH male and female) and Milan (MHS male) hypertensive rats. Five week old normotensive rats (LN and MNS) were transplanted with the parathyroid glands of LH and MHS rats immediately after parathyroidectomy (PTX). Plasma calcium fell rapidly after PTX but returned to physiological levels, confirming the functional activity of the graft. Systolic blood pressures of transplanted rats were significantly higher than normotensive LN and MNS controls. These results confirm the role of the parathyroid glands in the genesis of hypertension in Lyon and Milan male and female rats. They suggest that PHF may be implicated in the hypertensive mechanisms of these two models of genetic hypertension.

Animals↗
PubMed1991

Effect of parathyroidectomy on development of hypertension and atrial responsiveness in spontaneous hypertensive rats.

1. In order to further clarify the relationships between parathyroid function and development of hypertension, the effects of parathyroidectomy (PTX) on blood pressure and on responsiveness of atria isolated from spontaneous hypertensive rats (SHR) were examined. 2. PTX was carried out in 6-week-old SHR and normotensive Wistar rats. The experiments were performed 2 weeks after surgery. 3. PTX reduced the plasma calcium concentration and decreased atrial calcium content in SHR. On the other hand, basal contractile force and beat frequency of isolated atria were higher in PTX SHR than in sham-operated SHR. In response to cumulative addition of isoprenaline, atria from PTX SHR displayed diminished inotropic and chronotropic responses compared with sham-operated SHR. Similar results were obtained in atria isolated from Wistar rats. When calcium sensitivity was studied in atria from Wistar rats, basal and isoprenaline-induced maximum contractile forces were higher in PTX group than in the sham-operated group. Nevertheless, basal and isoprenaline-induced maximum contractile forces, determined at the respective plasma ionized calcium concentration of PTX and sham-operated groups (0.83 and 1.22 mmol/L), were not significantly different. 4. Our results do not favour a role for alteration in atrial activity as a causal mechanism in delayed development of experimental genetic hypertension after parathyroidectomy.

Animals↗
PubMed1991

Calcium metabolism in the Lyon hypertensive rat.

In order to define relationships between hypertension and calcium metabolism, we have studied calcium metabolism in Lyon genetically hypertensive rats (LH) and their two normotensive controls (LN and LL). The total and ionized plasma calcium levels were slightly but significantly decreased in the LH compared to LN and LL from 4 to 23 weeks of age. During this period, dietary calcium intake was decreased in LH rats but urinary and fecal excretions did not differ. Intestinal utilization and balance were impaired during development of hypertension in LH rats. Thus minor alterations in calcium metabolism differentiate the LH rat from its normotensive controls.

Aging↗
PubMed1990

Dietary calcium, vascular reactivity, and genetic hypertension in the Lyon rat strain.

In order to examine the relationship existing between dietary calcium and the development of hypertension, we developed a long-term study in the Lyon hypertensive rat strain (LH) and two control strains, the Lyon normotensive (LN) and low blood pressure rats (LL) given enriched (HCa, 2.5%), deprived (LCa, 0.03%) and normal (NCa, 0.6%) calcium diets. Evolution of body weight, systolic blood pressure (BP), plasma calcium and magnesium was monitored from 4 to 23 weeks of age. Total cardiovascular reactivity and contractile response of isolated aorta to norepinephrine were measured at 23 weeks of age. LH rats on HCa diet failed to develop hypertension (BP less than 150 mm Hg) whereas LH rats on LCa diet exhibited higher blood pressure levels than their controls fed the NCa diet. Moreover, in LN rats HCa diet slightly decreased BP whereas LCa had no effect. In the LL rats, on the contrary, only LCa diet slightly increased BP. In vivo responsiveness to NE was significantly higher in LH compared to LL and LN rats fed a NCa diet. HCa and LCa diets both induced a significant decrease in this response in LH rats. HCa diet increased the response in LN rats but decreased it in LL. In contrast, at the same age, the in vitro contractile response of isolated aorta to NE was significantly decreased in LH compared to LN and LL rats receiving NCa diet. Moreover in LH and LN rats on HCa diet the contractile response was markedly increased but no significant difference was observed with LCa diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Parathyroidectomy in the Lyon hypertensive rat: cardiovascular reactivity and aortic responsiveness.

We have studied the effect of parathyroidectomy on the systolic blood pressure, cardiovascular reactivity and the contractile response of isolated aorta to norepinephrine in the genetically hypertensive Lyon rat strain (LH), parathyroidectomized hypertensive Lyon rats (LH-PTX) and parathyroidectomized hypertensive Lyon rats given a Ca-enriched diet to re-establish normocalcemia (LH-PTX + Ca). Parathyroidectomy significantly lessened (-20%) the development of elevated blood pressure. In the LH-PTX + Ca, the blood pressure was lower than that of LH controls but was higher than that of LH-PTX. At 23 weeks, in vivo responsiveness to norepinephrine and angiotensin II was significantly lower in the LH-PTX and only slightly decreased in the LH-PTX + Ca. In contrast, at the same age, the in vitro contractile response of isolated aortas to norepinephrine was significantly higher in the LH-PTX compared with other groups. Interestingly, without endothelium, this difference disappeared. In conclusion, parathyroidectomy lessened the blood pressure elevation in the Lyon model of hypertensive rats via mechanisms that are partly independent of serum calcium levels.

Animals↗
PubMed1989

Parathyroid hormone acute vascular effect is mediated by decreased Ca2+ uptake and enhanced cAMP level.

Cardiovascular effects of parathyroid hormone (PTH) have been recently described. Pharmacological doses of PTH both reduce arterial pressure and increase blood flow of vascular beds. Two possible cellular mechanisms were investigated: (a) transmembrane Ca2+ fluxes and (b) cyclic AMP response in vascular smooth muscle. In vivo, results in the rat show that injection of synthetic bovine 1-34 fragment of PTH (bPTH-(1-34] produced a rapid (1-2 min) but transient (5-16 min) hypotensive effect which was dose-related (0.4-4 nmol.kg-1). In the in vitro studies on isolated rat aorta, bPTH-(1-34) partially inhibited noradrenaline (NA)-induced contractions by decreasing the sustained tonic component dependent on extracellular Ca2+. bPTH-(1-34) also produced relaxation of aorta preconstricted with NA or prostaglandin F2 alpha. Measurements of the lanthanum-resistant Ca2+ pool using 45Ca2+ showed that bPTH-(1-34) decreased basal Ca2+ uptake and partially inhibited Ca2+ uptake stimulated by NA or K+-depolarizing solution in a concentration-dependent fashion. In addition, bPTH-(1-34) caused a concentration-related increase in cyclic AMP in rat isolated aortic tissues. Hypotensive and vasorelaxing effects of bPTH-(1-34) thus appear to be mediated by a decrease in the amount of Ca2+ available for contraction and by an increase in cyclic AMP response in vascular smooth muscle cells.

Adenylyl Cyclases↗
PubMed1989

Intracellular Ca2+ and force determined simultaneously in isolated resistance arteries.

A method is described for the simultaneous measurement of intracellular Ca2+ ([Ca2+]i) and force generation in isolated resistance arteries using the fluorescent Ca2+ indicator fura-2. Branch II mesenteric resistance arteries were isolated from 12-wk-old Wistar-Kyoto rats and mounted in a wire myograph. The myograph was placed on the stage of a compound microscope interfaced with a dual excitation wavelength fluorometer, and the tissue was loaded with fura-2 by incubation over a 30-min period with the cell-permeable form of the dye. When stimulated with physiological salt solution containing 100 mM KCl and 10 microM norepinephrine, a rapid and transient increase in [Ca2+], was observed to precede active force development and plateau at approximately 60% of the maximal level after 50 s. Washout of the agonists induced relaxation of these small arteries, consisting of an 85% decline in active tension over 100 s and a fall in [Ca2+]i to 50% of prerelaxation level over the same time period. Forskolin (1 microM), which increases intracellular adenosine 3',5'-cyclic monophosphate, induced a 50% relaxation over a 150-s period that was preceded by a fall in [Ca2+]i. Nearly identical results were obtained with 100 microM sodium nitroprusside, which stimulates intracellular guanosine 3',5'-cyclic monophosphate production. These findings indicate that the initiating event of forskolin- and sodium nitroprusside-induced relaxation may be a reduction of [Ca2+]i. The method described is useful for examining basic physiological events and Ca2+-related mechanisms of action of vasoactive compounds in isolated resistance arteries.

Animals↗
PubMed1987

Effect of parathyroid hormone and antagonist on aortic cAMP levels.

Experiments were designed to further investigate the vasoactive mechanisms of parathyroid hormone (PTH) on vascular smooth muscle cells. Time courses of the cAMP responses to the fragment (1-34) of bovine PTH (bPTH(1-34)) on cAMP levels have been studied in rat isolated aorta and in aortic myocytes in primary culture. In both aorta and myocytes bPTH (1-34) induced an increase in cAMP levels that was maximal and reached, respectively, 1.6- and 1.9-fold the basal level after 2 min of contact with bPTH (1-34). The effect of bPTH (1-34) on aortic cAMP content was concentration dependent in the range of 30-300 nM. (Nle8,18, Tyr34)-bPTH (3-34)amide, an antagonist of bPTH (1-34) with a stimulant effect on renal and vascular adenylate cyclase activity, inhibited the cAMP-increasing effect of bPTH (1-34). These results are in favour of a role for cAMP in the vasodilating effect of PTH.

Animals↗
PubMed1986

Parathyroidectomy, cardiovascular reactivity and calcium distribution in aorta and heart of spontaneously hypertensive rats.

In order to elucidate the mechanisms by which parathyroidectomy (PTX), performed in young spontaneously hypertensive rats (SHR), delays the development and attenuates the level of hypertension, we studied, in vivo, cardiovascular reactivity (CVR, blood pressure response to bolus noradrenaline administration), aortic calcium distribution and cardiac calcium content in SHR with or without parathyroid glands. PTX was performed in 6-week-old animals and experiments were done in pretreated anaesthetized animals 2 and 22 weeks after surgery. A significantly decreased CVR was observed 22 weeks after PTX in SHR-PTX as compared with controls. These data are not specific for hypertensive animals since similar data are also obtained on normotensive Wistar rats treated in an identical fashion. In addition, after PTX in SHR and Wistar rats myocardial (auricle and ventricle) calcium content was more rapidly reduced (after 2 weeks) than aortic membrane-bound and cellular calcium fractions. The present studies established that PTX decreased CVR and alters calcium content and distribution in the cardiovascular systems of rats from hypertensive and normotensive strains. Furthermore, the results confirm a requirement for the parathyroid glands in the pathogenesis of spontaneous hypertension in SHR and for the normal CVR.

Animals↗
PubMed1985

Angiotensin II enhances calcium exchanges in isolated rat aorta.

The effect of angiotensin II (AII) on calcium exchanges in isolated rat aorta was investigated using the 45Ca lanthanum technique. AII induced a rapid (10 s) and long-lasting (120 min) increase of calcium uptake and enhanced calcium release for a short period. AII-stimulated calcium uptake was antagonized by saralasin and verapamil but not by indomethacin. These data indicate that AII increases rat aortic calcium exchanges via receptor-operated and voltage-dependent calcium channels.

Angiotensin II↗
PubMed1985

[Dietary calcium and arterial hypertension in the rat].

The effect of diets modified with respect to their calcium content was studied in three models of hypertensive rats: mineralocorticoid hypertension, DOCA + saline rats and genetic hypertension, SHR and LH rats. Normocalcemic control diet, was equilibrated in vitamins and contained 0.6 p. 100 Ca, 0.24 p. 100 Na and 0.6 p. 100 K. Low calcium diet with only 0.03 p. 100 Ca was studied in the SHR from 5 to 10 weeks of age. Calcium enriched diets contained 1.3, 1.2 and 2.5 p. 100 calcium respectively for DOCA (6 to 16 weeks), SHR (5 to 44 weeks) and LH (female rats, 4 to 22 weeks). In the SHR low calcium diet enhanced hypertension. At the opposite in the three models, calcium enriched diet lessened hypertension. The effect appeared within 2 weeks and was long lasting. These results clearly establish that in young hypertensive rat a low calcium diet enhances the development of hypertension and confirm earlier works with calcium enriched diets. Experimental and clinical data from other groups leads us to emphasize the importance of alimentary calcium in the hypertensive pathology.

Animals↗
PubMed1984

Distribution of parathyroid hormone-sensitive adenylate cyclase in isolated rabbit renal cortex microvessels and glomeruli.

The effect of the synthetic amino-terminal fragment of bovine parathyroid hormone, bPTH-(1-34), on the adenylate cyclase of microvessels and glomeruli isolated from rabbit kidney cortex was studied in the presence and absence of guanosine triphosphate (GTP). bPTH-(1-34) stimulated the vascular and glomerular adenylate cyclase in a dose-dependent manner with apparent ED50 values of 11.5 nM and 64 nM respectively, in the absence of GTP. 10(-4)M GTP greatly amplified the vascular response to bPTH-(1-34) while, in the glomeruli, both GTP and bPTH-(1-34) had only additive effects. In the presence of GTP, vascular and glomerular apparent ED50 were 190 nM and 64 nM respectively. [Nle8, Nle18, Tyr34] -bPTH-(3-34) amide, described as a PTH antagonist, inhibited the action of bPTH-(1-34) in the microvessels and to a lesser extent in the glomeruli. PTH is therefore a potent stimulator of adenylate cyclase in rabbit renal microvessels and glomeruli, and may play a role in the regulation of renal blood flow and glomerulo-tubular feedback control.

Adenylyl Cyclases↗
PubMed1984

Low calcium diet enhances development of hypertension in the spontaneously hypertensive rat.

Young (5 week old) spontaneously hypertensive rats (SHR) were fed diets modified with respect to their calcium content. Control rats were given a normal calcium diet (0.3 per cent). During the experiment the systolic blood pressure (SBP), heart rate and serum level of total and ionized calcium were measured. Three diets were studied :calcium-free diet (0 per cent, h1), low calcium diet (0.03 per cent, h2) and high calcium diet (1.2 per cent, H). The h1 diet induced a transitory increase (at week 2), then a long-lasting decrease in SBP for 12 weeks. Heart rate and calcemia were significantly decreased. The h2 diet enhanced the increase in SBP and lowered heart rate for 10 weeks. Level of total and ionized serum calcium were unchanged. The high calcium diet (1.2 per cent) attenuated the increase in SBP for 44 weeks and enhanced the heart rate for 16 weeks. The serum level of total calcium remained stable but that of ionized calcium increased significantly at week 7. These data clearly establish that, in young SHR, a low calcium diet enhances the development of genetic hypertension and confirm earlier works obtained with calcium enriched diets. Experimental and clinical data lead us to emphasize the importance of alimentary calcium in the hypertensive pathology.

Animals↗